tbuckley/cabot-search huggingface dataset:
Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C
Authors: Kazuhiko Mishima, Ryo Nishikawa, Yoshitaka Narita, Junki Mizusawa, Minako Sumi, Tomoyuki Koga, Nobuyoshi Sasaki, Manabu Kinoshita, Motoo Nagane, Yoshiki Arakawa, Koji Yoshimoto, Ichiyo Shibahara, Naoki Shinojima, Kenichiro Asano, Takao Tsurubuchi, Hikaru Sasaki, Akio Asai, Takashi Sasayama, Yasutomo Momii, Atsushi Sasaki, Shigeo Nakamura, Masaru Kojima, Jun-ichi Tamaru, Kazuhiro Tsuchiya, Miho Gomyo, Kayoko Abe, Manabu Natsumeda, Fumiyuki Yamasaki, Hiroshi Katayama, Haruhiko Fukuda
Journal: Neuro-Oncology (2022)

The goal was to determine whether the addition of temozolomide (TMZ) to the standard treatment of high-dose methotrexate (HD-MTX) and whole-brain radiotherapy (WBRT) for primary central nervous system lymphoma (PCNSL) improves survival.An open-label, randomized, phase III trial was conducted in Japan, enrolling immunocompetent patients aged 20-70 years with histologically confirmed, newly diagnosed PCNSL. After administration of HD-MTX, patients were randomly assigned to receive WBRT (30 Gy) ± 10 Gy boost (arm A) or WBRT ± boost with concomitant and maintenance TMZ for 2 years (arm B). The primary endpoint was overall survival (OS).Between September 29, 2014 and October 15, 2018, 134 patients were enrolled, of whom 122 were randomly assigned and analyzed. At the planned interim analysis, 2-year OS was 86.8% (95% confidence interval [CI]: 72.5-94.0%) in arm A and 71.4% (56.0-82.2%) in arm B. The hazard ratio was 2.18 (95% CI: 0.95-4.98), with the predicted probability of showing the superiority of arm B at the final analysis estimated to be 1.3%. The study was terminated early due to futility. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was measured in 115 tumors, and it was neither prognostic nor predictive of TMZ response.This study failed to demonstrate the benefit of concomitant and maintenance TMZ in newly diagnosed PCNSL.
The Impacts of Paid Family and Medical Leave on Worker Health, Family Well-Being, and Employer Outcomes
Authors: Ann Bartel, Maya Rossin-Slater, Christopher Ruhm, Meredith Slopen, Jane Waldfogel
Journal: Annual Review of Public Health (2022)

This article reviews the evidence on the impacts of paid family and medical leave (PFML) policies on workers’ health, family well-being, and employer outcomes. While an extensive body of research demonstrates the mostly beneficial effects of PFML taken by new parents on infant, child, and parental health, less is known about its impact on employees who need leave to care for older children, adult family members, or elderly relatives. The evidence on employers is similarly limited but indicates that PFML does not impose major burdens on them. Taken together, the evidence suggests that PFML policies are likely to have important short- and long-term benefits for population health, without generating large costs for employers. At thesame time, further research is needed to understand the effects of different policy parameters (e.g., wage replacement rate and leave duration) and of other types of leave beyond parental leave.
Ipilimumab plus decitabine for patients with MDS or AML in posttransplant or transplant-naïve settings
Authors: Jacqueline S. Garcia, Yael Flamand, Livius Penter, Michael Keng, Benjamin K. Tomlinson, Lourdes M. Mendez, Paul Koller, Nicole Cullen, Yohei Arihara, Kathleen Pfaff, Jacquelyn O. Wolff, Andrew M. Brunner, Ilene Galinsky, Asad Bashey, Joseph H. Antin, Corey Cutler, Vincent Ho, Brian A. Jonas, Marlise R. Luskin, Martha Wadleigh, Eric S. Winer, Alexandra Savell, Rebecca Leonard, Taylor Robertson, Matthew S. Davids, Howard Streicher, Scott J. Rodig, Jerome Ritz, Catherine J. Wu, Daniel J. DeAngelo, Donna Neuberg, Richard M. Stone, Robert J. Soiffer
Journal: Blood (2022)

Two articles in this week’s issue focus on the use of ipilimumab and decitabine for patients with myelodysplasia (MDS) and acute myeloid leukemia (AML) before and after hematopoietic stem cell transplantation (HSCT) for high-risk disease. In the first article, Garcia et al report on the results of a phase 1 trial of the combination in 54 patients, demonstrating overall response rate of 52% in patients who are HSCT-naïve and 20% in patients post-HSCT; responses are usually short-lived. In the second article, Penter and colleagues characterize gene expression responses to therapy and conclude that decitabine acts directly to clear leukemic cells while ipilimumab acts on infiltrating lymphocytes in marrow and extramedullary sites. Responses are determined by leukemic cell burden and by the frequency and phenotype of infiltrating lymphocytes. Increasing bone marrow regulatory T cells is identified as a potential contributor to checkpoint inhibitor escape.
Thresholds of handgrip strength for all-cause, cancer, and cardiovascular mortality: A systematic review with dose-response meta-analysis
Authors: Rubén López-Bueno, Lars Louis Andersen, Ai Koyanagi, Rodrigo Núñez-Cortés, Joaquín Calatayud, José Casaña, Borja del Pozo Cruz
Journal: Ageing Research Reviews (2022)

While handgrip strength is associated with all-cause and cause-specific mortality, whether such associations are dose-dependent is largely unknown. Therefore, we conducted a systematic review on the dose-response relationship of handgrip strength with all-cause mortality, cancer, and cardiovascular mortality.The data source included three electronic databases (PubMed/MEDLINE, Web of Science and Scopus) from inception to 8 February 2022. Prospective cohort studies of healthy adults with objective measures of handgrip strength were included. Two researchers independently screened studies, extracted data, and assessed risk of bias. We used estimates regarding handgrip strength categories to conduct a random forest model, and a two-stage random-effects hierarchical meta-regression model pooling study-specific estimates for dose-response relationship. Outcomes included all-cause, cancer, and cardiovascular mortality.Forty-eight studies comprising 3,135,473 participants (49.6% women, age range 35-85 years) were included. Random forest models showed a significant inverse association between handgrip strength and all-cause and cause-specific mortality. Dose-response meta-analyses showed that higher levels of handgrip strength significantly reduced the risk of all-cause mortality within 26-50 kg (Higgin´s I2 =45.7%) in a close-to-linear inverse fashion. Cancer and cardiovascular mortality displayed a trend towards a U-shaped association with a significant risk reduction between 16 and 33 kg (Higgin´s I2 =77.4%), and a close-to-linear inverse shaped and significant risk reduction ranging from 24 to 40 kg (Higgin´s I2 =79.7%) respectively.There is strong evidence for an association between lower handgrip strength with higher all-cause, cancer, and cardiovascular mortality risk. The dose-response relationship of handgrip strength substantially varies depending on the cause of mortality.
EBV-driven lymphoid neoplasms associated with pediatric ALL maintenance therapy
Authors: Sarah Elitzur, Ajay Vora, Birgit Burkhardt, Hiroto Inaba, Andishe Attarbaschi, Andre Baruchel, Gabriele Escherich, Brenda Gibson, Hsi-Che Liu, Mignon Loh, Anthony V. Moorman, Anja Möricke, Rob Pieters, Anne Uyttebroeck, Susan Baird, Jack Bartram, Shlomit Barzilai-Birenboim, Sandeep Batra, Miriam Ben-Harosh, Yves Bertrand, Trudy Buitenkamp, Kenneth Caldwell, Ricardo Drut, Ashley V. Geerlinks, Gil Gilad, John Grainger, Stephanie Haouy, Nicholas Heaney, Mary Huang, Danielle Ingham, Zdenka Krenova, Michaela Kuhlen, Thomas Lehrnbecher, Atsushi Manabe, Felix Niggli, Claudia Paris, Shoshana Revel-Vilk, Pierre Rohrlich, Mohamad G. Sinno, Tomasz Szczepanski, Melanie Tamesberger, Rajasekharan Warrier, Matthias Wolfl, Ronit Nirel, Shai Izraeli, Arndt Borkhardt, Kjeld Schmiegelow
Journal: Blood (2022)
Updates in intraoperative strategies for enhancing intra-axial brain tumor control
Authors: Adela Wu, Janet Yuling Wu, Michael Lim
Journal: Neuro-Oncology (2022)

Abstract To ensure excellent postoperative clinical outcomes while preserving critical neurologic function, neurosurgeons who manage patients with intra-axial brain tumors can use intraoperative technologies and tools to achieve maximal safe resection. Neurosurgical oncology revolves around safe and optimal extent of resection, which further dictates subsequent treatment regimens and patient outcomes. Various methods can be adapted for treating both primary and secondary intra-axial brain lesions. We present a review of recent advances and published research centered on different innovative tools and techniques, including fluorescence-guided surgery, new methods of drug delivery, and minimally invasive procedural options.
Effects of exercise interventions on executive function in old adults with mild cognitive impairment: A systematic review and meta-analysis of randomized controlled trials
Authors: Miaoran Lin, Chuyi Ma, Jingfang Zhu, Jiahui Gao, Li Huang, Jia Huang, Zhizhen Liu, Jing Tao, Lidian Chen
Journal: Ageing Research Reviews (2022)
Comprehensive analysis of human IL‐4 receptor subunits shows compartmentalization in steady state and dupilumab treatment
Authors: Lukas E. M. Heeb, Onur Boyman
Journal: Allergy (2022)

Insight into the pathomechanism of atopic diseases demonstrated a pivotal role of the cytokines interleukin-4 (IL-4) and IL-13, which has spurred the development of tailored therapeutics targeting their common IL-4 receptor (IL-4R). However, several aspects of the IL-4R system remain ill-defined in humans.We used multicolor spectral flow cytometry to characterize IL-4R subunit expression in 28 human immune cell subsets on protein and mRNA levels and assessed their subcellular distribution by applying a specifically adapted protocol that avoided influence of fixation and permeabilization on fluorochrome and antibody performance. In patients, we investigated possible changes in IL-4Rα distribution before and during treatment with dupilumab, a monoclonal antibody-targeting IL-4Rα.Whereas all immune cell subsets investigated expressed IL-4Rα and common γ chain protein and mRNA, expression of IL-13Rα1 was restricted to myeloid and B cells. Interestingly, some cells contained considerably more intracellular IL-4R protein than on their surface. Naive B cells were found to carry the highest levels of IL-4Rα distributed evenly between surface and intracellular space, whereas IL-4Rα was found predominantly in intracellular pools in neutrophils. In patients with atopic diseases treated with dupilumab, we observed that engagement of IL-4Rα by dupilumab resulted in internalization of the antibody and decreased total IL-4Rα expression. Notably, even after months of treatment not all intracellular IL-4Rα molecules were occupied by dupilumab, indicating the presence of a "dormant" intracellular IL-4Rα pool that could be mobilized upon certain extrinsic or intrinsic cues.Collectively, our findings suggest that distinct human immune cell subsets contain surface and intracellular IL-4R pools, which are differently affected by targeted biologic treatment.
Social and Psychosocial Determinants of Racial and Ethnic Differences in Cardiovascular Health in the United States Population
Authors: Nilay S. Shah, Xiaoning Huang, Lucia C. Petito, Michael P. Bancks, Hongyan Ning, Natalie A. Cameron, Kiarri N. Kershaw, Namratha R. Kandula, Mercedes R. Carnethon, Donald M. Lloyd-Jones, Sadiya S. Khan
Journal: Circulation (2022)

Background: Social and psychosocial factors are associated with cardiovascular health (CVH). Our objective was to examine the contributions of individual-level social and psychosocial factors to racial and ethnic differences in population CVH in the NHANES (National Health and Nutrition Examination Surveys) 2011 to 2018, to inform strategies to mitigate CVH inequities. Methods: In NHANES participants ages ≥20 years, Kitagawa-Blinder-Oaxaca decomposition estimated the statistical contribution of individual-level factors (education, income, food security, marital status, health insurance, place of birth, depression) to racial and ethnic differences in population mean CVH score (range, 0–14, accounting for diet, smoking, physical activity, body mass index, blood pressure, cholesterol, blood glucose) among Hispanic, non-Hispanic Asian, or non-Hispanic Black adults compared with non-Hispanic White adults. Results: Among 16 172 participants (representing 255 million US adults), 24% were Hispanic, 12% non-Hispanic Asian, 23% non-Hispanic Black, and 41% non-Hispanic White. Among men, mean (SE) CVH score was 7.45 (2.3) in Hispanic, 8.71 (2.2) in non-Hispanic Asian, 7.48 (2.4) in non-Hispanic Black, and 7.58 (2.3) in non-Hispanic White adults. In Kitagawa-Blinder-Oaxaca decomposition, education explained the largest component of CVH differences among men (if distribution of education were similar to non-Hispanic White participants, CVH score would be 0.36 [0.04] points higher in Hispanic, 0.24 [0.04] points lower in non-Hispanic Asian, and 0.23 [0.03] points higher in non-Hispanic Black participants; P &lt;0.05). Among women, mean (SE) CVH score was 8.03 (2.4) in Hispanic, 9.34 (2.1) in non-Hispanic Asian, 7.43 (2.3) in non-Hispanic Black, and 8.00 (2.5) in non-Hispanic White adults. Education explained the largest component of CVH difference in non-Hispanic Black women (if distribution of education were similar to non-Hispanic White participants, CVH score would be 0.17 [0.03] points higher in non-Hispanic Black participants; P &lt;0.05). Place of birth (born in the United States versus born outside the United States) explained the largest component of CVH difference in Hispanic and non-Hispanic Asian women (if distribution of place of birth were similar to non-Hispanic White participants, CVH score would be 0.36 [0.07] points lower and 0.49 [0.16] points lower, respectively; P &lt;0.05). Conclusions: Education and place of birth confer the largest statistical contributions to the racial and ethnic differences in mean CVH score among US adults.
Author Correction: Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus
Authors: Andreas Mackensen, Fabian Müller, Dimitrios Mougiakakos, Sebastian Böltz, Artur Wilhelm, Michael Aigner, Simon Völkl, David Simon, Arnd Kleyer, Luis Munoz, Sascha Kretschmann, Soraya Kharboutli, Regina Gary, Hannah Reimann, Wolf Rösler, Stefan Uderhardt, Holger Bang, Martin Herrmann, Arif Bülent Ekici, Christian Buettner, Katharina Marie Habenicht, Thomas H. Winkler, Gerhard Krönke, Georg Schett
Journal: Nature Medicine (2022)
Elucidating the neurological mechanism of the FLASH effect in juvenile mice exposed to hypofractionated radiotherapy
Authors: Barrett D Allen, Yasaman Alaghband, Eniko A Kramár, Ning Ru, Benoit Petit, Veljko Grilj, Michael S Petronek, Casey F Pulliam, Rachel Y Kim, Ngoc-Lien Doan, Janet E Baulch, Marcelo A Wood, Claude Bailat, Douglas R Spitz, Marie-Catherine Vozenin, Charles L Limoli
Journal: Neuro-Oncology (2022)

Ultrahigh dose-rate radiotherapy (FLASH-RT) affords improvements in the therapeutic index by minimizing normal tissue toxicities without compromising antitumor efficacy compared to conventional dose-rate radiotherapy (CONV-RT). To investigate the translational potential of FLASH-RT to a human pediatric medulloblastoma brain tumor, we used a radiosensitive juvenile mouse model to assess adverse long-term neurological outcomes.Cohorts of 3-week-old male and female C57Bl/6 mice exposed to hypofractionated (2 × 10 Gy, FLASH-RT or CONV-RT) whole brain irradiation and unirradiated controls underwent behavioral testing to ascertain cognitive status four months posttreatment. Animals were sacrificed 6 months post-irradiation and tissues were analyzed for neurological and cerebrovascular decrements.The neurological impact of FLASH-RT was analyzed over a 6-month follow-up. FLASH-RT ameliorated neurocognitive decrements induced by CONV-RT and preserved synaptic plasticity and integrity at the electrophysiological (long-term potentiation), molecular (synaptophysin), and structural (Bassoon/Homer-1 bouton) levels in multiple brain regions. The benefits of FLASH-RT were also linked to reduced neuroinflammation (activated microglia) and the preservation of the cerebrovascular structure, by maintaining aquaporin-4 levels and minimizing microglia colocalized to vessels.Hypofractionated FLASH-RT affords significant and long-term normal tissue protection in the radiosensitive juvenile mouse brain when compared to CONV-RT. The capability of FLASH-RT to preserve critical cognitive outcomes and electrophysiological properties over 6-months is noteworthy and highlights its potential for resolving long-standing complications faced by pediatric brain tumor survivors. While care must be exercised before clinical translation is realized, present findings document the marked benefits of FLASH-RT that extend from synapse to cognition and the microvasculature.
Superwetting Injectable Hydrogel with Ultrastrong and Fast Tissue Adhesion for Minimally Invasive Hemostasis
Authors: Congying Wei, Weili Shi, Chuangqi Zhao, Shuai Yang, Jiajia Zheng, JinPan Zhong, Tianyi Zhao, Simin Kong, Xi Gong, Mingjie Liu
Journal: Advanced Healthcare Materials (2022)

Injectable hydrogels have recently emerged as alternatives to sutures for various clinical indications. However, existing injectable hydrogels are unsuitable for hemostasis in minimally invasive surgery because of their weak interfacial adhesion and complex/prolonged processing. Herein, a superwetting injectable hydrogel composed of oppositely charged polysaccharides is developed. The spontaneous spreading of the injectable hydrogel on the surfaces achieves complete wetting and forms tight interfacial contact by absorbing the interfacial water. The superwetting ability and subsequent covalent crosslinking perform fast and ultrastrong wet adhesion (140 kPa) on the tissue surface. Ex vivo porcine and in vivo rat models show that the hydrogel successfully leads to the aggregation of erythrocytes for targeted hemostasis (in less than 12 s) without requiring external adjuncts, and no postsurgical adhesions to the peripheral tissues. This further demonstrates that hydrogel can act as an effective hemostasis agent in laparoscopic surgery in a rabbit model. Overall, the strong wet adhesion, antibacterial properties, and easy operability make this injectable hydrogel a promising candidate for hemostasis applications, as it can successfully combine clinical efficacy and transformation opportunities for minimally invasive surgery.
The Fibrates Story — A Tepid End to a PROMINENT Drug
Authors: Salim S Virani
Journal: New England Journal of Medicine (2022)

Pemafibrate is a selective peroxisome proliferator–activated receptor α modulator that has putative greater triglyceride-lowering and high-density lipoprotein (HDL) cholesterol–raising properties than other fibrates.1 Now in the Journal, Das Pradhan et al.2 describe the results of the Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT) trial. In this trial, 10,497 patients with type 2 diabetes, a triglyceride level between 200 and 499 mg per deciliter, and an HDL cholesterol level of 40 mg per deciliter or less were randomly assigned to receive 0.2-mg tablets of pemafibrate twice daily or placebo. In the PROMINENT trial, two cohorts . . .
Abstract 14100: Which Sodium-Glucose Cotransporter 2 Inhibitors Agent is More Effective in Patients With Heart Failure? A Systematic Review and Network Meta-Analysis of Randomized Clinical Trials
Authors: Ahmed K. Awad, Mohammed Tarek Hasan, Mohamed Shih, Amir N. Attia, Heba Aboeldahab, Basel Abdelazeem, Nischit Baral, pramod savarapu, Annabelle S Santos Volgman
Journal: Circulation (2022)

Background: Treatment with various sodium-glucose cotransporter 2 inhibitors (SGLT-2Is) has decreased cardiovascular events in patients with heart failure (HF). Therefore, we conducted a network meta-analysis to investigate which SGLT-2Is are more effective in patients with HF. Methods: PubMed, Web of Science, Scopus, and Embase, were systematically searched from inception to February 2022. We included randomized controlled trials (RCTs) that investigated the use of SGLT-2Is vs. placebo in HF patients. The main outcomes were all-cause, cardiovascular mortality, serious adverse events, and hospitalizations due to HF. The random-effects method model and inverse variance statistics were used to calculate the odds ratio (OR) with a 95% confidence interval (CI). Results: Our study included 12 RCTs with a total number of 69,024 patients (37,923 in the SGLT2 inhibitors group and 31,101 in the placebo group). Five RCTs used empagliflozin, 4 used dapagliflozin, 1 used canagliflozin, 1 used ertugliflozin, and 1 used sotagliflozin. Our analysis showed that empagliflozin has a statistically significant lowest odds for both cardiovascular mortality and serious adverse effects (OR: 0.80 with 95% CI [0.67-0.96]) and (OR: 0.84 with 95% CI [0.76-0.93]), respectively compared to other SGLT-2Is. All SGLT-2Is have been associated with the same lower odds without preferences for one over the others regarding all-cause mortality. Furthermore, the hospitalization rate due to HF showed a statistically significant decrease with all the SGLT-2Is except for canagliflozin, which showed insignificant results with (OR: 0.63 with 95% CI [0.39-1.01]). Conclusion: No differences between the SGLT-2Is included in this analysis were observed in terms of all-cause mortality. Empagliflozin had the lowest odds of cardiovascular mortality and serious adverse effects. Canagliflozin was the only SGLT-2Is that showed no significant results in odds of hospitalization for HF.
Outcomes of first therapy after CD19-CAR-T treatment failure in large B-cell lymphoma
Authors: Ana Alarcon Tomas, Joshua A. Fein, Shalev Fried, Jessica R. Flynn, Sean M. Devlin, Warren B. Fingrut, Theodora Anagnostou, Anna Alperovich, Nishi Shah, Ellen Fraint, Richard J. Lin, Michael Scordo, Connie Lee Batlevi, Michal J. Besser, Parastoo B. Dahi, Ivetta Danylesko, Sergio Giralt, Brandon S. Imber, Elad Jacoby, Meirav Kedmi, Arnon Nagler, M. Lia Palomba, Mikhail Roshal, Gilles A. Salles, Craig Sauter, Noga Shem-Tov, Avichai Shimoni, Joachim Yahalom, Ronit Yerushalmi, Gunjan L. Shah, Abraham Avigdor, Miguel-Angel Perales, Roni Shouval
Journal: Leukemia (2022)
Hollow copper sulfide nanoparticles carrying ISRIB for the sensitized photothermal therapy of breast cancer and brain metastases through inhibiting stress granule formation and reprogramming tumor‐associated macrophages
Authors: Fan Tong, Haili Hu, Yanyan Xu, Yang Zhou, Rou Xie, Ting Lei, Yufan Du, Wenqin Yang, Siqin He, Yuan Huang, Tao Gong, Huile Gao
Journal: Acta Pharmaceutica Sinica B (2022)

As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.